Biomedical subjects

L A Carlson

Publications and source records attributed to L A Carlson.

At least 55 records · Page 3Linked to original sources

PubMed1989

Long-term effect of pindolol on lipids and lipoproteins in men with newly diagnosed hypertension.

This is the first long-term study of pindolol in a population-based sample of men with newly diagnosed hypertension. Eighty-two patients, with a diastolic pressure of 100 mm Hg or more, were identified after screening 6000 men. Many patients were overweight. 82 population controls, matched by sex, age and body mass index, were also recruited. Fourty-eight per cent of the patients and 25% of the controls had a family history of hypertension. Serum triglyceride and urate values were higher in patients than controls at the baseline investigation. Seventy-four patients were followed for 1 year. The dose of pindolol averaged 7.7 mg once daily after 1 year. The diastolic blood pressure was reduced by 13.4 mm Hg. The target pressure of 95 mm Hg or less was achieved in 89% of the patients. The HDL-cholesterol concentration was normal and did not change, whereas the LDL-cholesterol concentration decreased by 0.15 mmol.l-1 during treatment. The total triglyceride values increased transiently up to 6 months, but no significant increase was seen after one year. It is concluded that pindolol had no adverse effect on serum cholesterol and its HDL- and LDL-fractions during 1 year of treatment.

Adult↗

PubMed1989

In-vitro lipolysis of small very low density lipoproteins from human plasma. Dependence of characteristics of end products on the serum triglyceride concentration.

Isolated, small very low density lipoproteins (VLDL) from males with plasma concentrations of VLDL triglycerides ranging between 0.92 and 8.65 mmol l-1 were incubated with lipoprotein lipase. There were no differences in the size of the VLDL particles isolated from normo-respectively hypertriglyceridaemic plasmas. After incubation, 4.5 +/- 3.5% (mean +/- SD) of the initial glyceride-glycerol remained in the incubate. This amount did not vary with the plasma VLDL concentration. The incubation mixture was separated into three density fractions: VLDL, low density lipoprotein (LDL) and a high density lipoprotein (HDL) respectively. The lipid contents of these were determined. The distribution of cholesterol and phospholipids after lipolysis was highly dependent on the plasma VLDL level. The amount of cholesterol and phospholipids recovered in the LDL density region increased with the rising plasma VLDL level, the correlation coefficients for this relationship were 0.80 and 0.66, respectively. The results thus indicate that small, similar size VLDL from normo-respectively hypertriglyceridaemic plasmas have different properties.

Adult↗

PubMed1989

Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid.

Thirty-one consecutive unselected hyperlipidaemic patients were treated daily with 4 g of nicotinic acid for 6 weeks. The concentrations in serum of lipoprotein Lp(a), and the major lipoprotein classes, were determined before and after the treatment. Nicotinic acid significantly reduced the serum levels of Lp(a) in the whole patient group. Linear regression analysis showed a strong negative relationship between the percentage reduction of Lp(a) and the serum triglyceride level before treatment (r = -0.78), which implied that for patients with a serum triglyceride concentration above 7.5 mmol l-1 there was a rise of Lp(a). The average individual percentage decrease of the concentration of Lp(a) was calculated after the exclusion of four patients who had serum triglyceride levels above 10 mmol l-1. The decrease was 38% with a 95% confidence interval of 28-47%. The absolute decrease of Lp(a) was correlated with the pretreatment levels of Lp(a) (r = 0.91). Within the whole group of patients there was a linear relationship between the percentage decrease of Lp(a) and that of LDL cholesterol (r = 0.88). This latter strong relationship might be due to an inhibition of the synthesis of the protein common to the two lipoproteins, apolipoprotein B.

Adult↗

PubMed1989

Concentrations of apolipoproteins B, C-I, C-II, C-III, E and lipids in serum and serum lipoproteins of normal subjects during alimentary lipaemia.

The effect of alimentary lipaemia, induced by ingestion of 100 g of fat (cream), on lipids and apolipoprotein B, C-I, C-II, C-III and E levels was evaluated in 16 normotriglyceridaemic subjects. Apolipoprotein concentrations were determined by enzyme immunoassay in whole serum and, in a subsample of seven subjects, in serum lipoprotein fractions of d less than 1.006 kg/l (supernatant) containing very low density lipoproteins (VLDL) and chylomicrons and of d greater than 1.006 kg/l (infranatant) containing low density lipoproteins (LDL) and high density lipoproteins (HDL). Triglyceride concentrations in the supernatant were increased by 164% 3 h after the fat ingestion. The level of alimentary lipaemia was positively related to the fasting serum concentrations of triglycerides and apolipoproteins C-II and C-III and inversely related to the fasting concentration of apolipoprotein E in the infranatant lipoprotein fraction with d greater than 1.006 kg/l. No significant changes in the serum levels of apolipoproteins B, C-I and E were found during the postprandial lipaemia. By contrast, serum concentrations of apolipoproteins C-II and C-III were decreased (compared to the fasting levels) 6 h after the fatty meal. In the 3-h samples all apolipoproteins were increased in the supernatant (VLDL + chylomicrons) and a corresponding decrease was observed in the infranatant (LDL + HDL). In conclusion, this study shows that in normotriglyceridaemic subjects a high serum level of apo C-II is not associated with a more rapid clearance of alimentary lipaemia than a low level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report.

The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.

Arteriosclerosis↗

PubMed1988

Normalization of high density lipoprotein in fish eye disease plasma by purified normal human lecithin: cholesterol acyltransferase.

Plasma from a patient with fish eye disease has been enriched with autologous high density lipoproteins (HDL) and supplemented with highly purified normal human plasma lecithin:cholesterol acyltransferase (LCAT). Incubation of such plasma at 37 C in vitro resulted in normalization of its low HDL cholesteryl ester percentage, from 23% to 79%, associated with a two-fold increase in both the cholesteryl ester and triglyceride contents of the HDL fraction, as compared to incubation experiments with absent or heat-inactivated purified normal LCAT. The normalization of the HDL cholesteryl ester percentage induced by incubation with purified normal LCAT also was accompanied by an increase in the size of the original fish eye disease HDL particles, which had a mean mass of 115 kd, to HDL particle populations with mean particle masses ranging from 130-220 kd, depending on the concentration of purified LCAT in the incubate. Both HDL cholesterol esterification and particle enlargement were abolished completely by the LCAT inhibitor DTNB and by heat inactivation of the purified normal LCAT. The results give further evidence that fish eye disease is an alpha-LCAT deficiency.

Aged↗

PubMed1988

Serum apolipoproteins, lipoproteins and fatty acids in relation to ischaemic heart disease in northern and southern European males.

Serum apolipoprotein and lipoprotein concentrations, fatty acid spectra of various lipids, dietary habits and common risk factors for ischaemic heart disease were studied in 73 and 77 randomly selected, 50-year-old healthy men in Naples and Stockholm, respectively. Mean serum cholesterol concentration was higher in Stockholm than in Naples men (6.23 vs. 5.47 mmol/l, p less than 0.001) as were low (LDL) (4.08 vs. 3.57 mmol/l, p less than 0.001) and high (HDL) (1.40 vs. 1.25 mmol/l, p less than 0.001) density lipoprotein fractions. Mean serum triglyceride concentrations did not differ. Mean apolipoprotein B and C-I concentrations were higher in Stockholm men (1,116 vs. 1,020 mg/l, p less than 0.05 and 96 vs. 79 mg/l, p less than 0.01, respectively). Stockholm men derived significantly more of their calories from fat (38 vs. 28%, p less than 0.001) and the dietary fat had significantly lower polyunsaturated-to-saturated fatty acid ratio (P/S-ratio 0.29 vs. 0.51, p less than 0.001), and less from carbohydrate (44 vs. 49%, p less than 0.001) than Naples men, respectively. Mean caloric intake and mean weight/height index did not differ. Stockholm men had higher blood pressures, but there were more smokers among Naples men. The higher fat intake in Stockholm men may offer an explanation of the differences seen in lipoprotein and apoprotein concentrations and compositions but other factors, such as genetic influences cannot be excluded. A greater cholesterol flux through the plasma compartment in Stockholm men may be one important factor contributing to the higher incidence of ischaemic heart disease in this population.

Adult↗

PubMed1988

Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid.

Consecutive survivors of a myocardial infarction from the Southern Hospital, below 70 years of age, were randomized into a Control group (n = 276) and a Treatment group (n = 279). The latter was openly prescribed the combination of clofibrate and nicotinic acid for serum lipid lowering. Each patient should remain in the study for 5 years and be seen regularly every 4 months at a special IHD outpatient clinic within the hospital. The concentration of serum cholesterol and triglyceride was lowered by 13% and 19%, respectively, in the Treatment group compared to the Control group. Total mortality was 82 cases in the Control group and 61 in the Treatment group, a 26% reduction (p less than 0.05). For patients above 60 years of age in the Treatment group the reduction in mortality was 28% (p less than 0.05). IHD mortality was reduced by 36% (p less than 0.01) in the Treatment group compared to the Control group. The beneficial effect of the serum lipid lowering treatment was related to the serum triglyceride concentration in two ways. First, it only occurred in patients with a triglyceride level greater than 1.5 mmol/l (n = 216). Secondly, it was most pronounced in the 44% of the treated patients who had a lowering of the serum triglyceride by 30% or more, and in this subgroup the reduction of IHD mortality was 60% (p less than 0.01). For serum cholesterol there were no such relations. The difference between serum triglycerides and cholesterol concerning these relations to the treatment outcome may be due to the fact that hypertriglyceridaemia was the most common hyperlipidaemia among our patients, occurring in 50%, while hypercholesterolaemia only occurred in 13%. Caution should be exercised in the interpretation of the results as the trial was not blind. However, the fact that the decrease in IHD deaths was directly related to the degree of serum triglyceride lowering indicates that it was the drug effect on serum lipids that was responsible for the beneficial effect of the treatment.

Aged↗

PubMed1988

Substrate specificity of plasma lecithin: cholesterol acyltransferase in abetalipoproteinemia.

The lecithin: cholesterol acyltransferase (LCAT) activity of lipoprotein-depleted plasma from a patient with abetalipoproteinemia has been assayed in a modified Glomset-Wright incubation system with three different normal lipoprotein substrates consisting of an authentic mixture of very low (VLDL), low (LDL) and high (HDL) density lipoproteins for the assay of total LCAT activity, HDL to assay alpha-LCAT activity and combined VLDL and LDL to assay beta-LCAT activity, respectively. Although reduced to about half the normal control values, both alpha- and beta-LCAT activities were present in the patient's plasma. It has been shown earlier that secretion of LCAT is linked to that of VLDL, but since patients with abetalipoproteinemia cannot form either chylomicrons or VLDL, our results suggest that a secretion of these triglyceride-rich lipoproteins do not seem to be a prerequisite for a basal secretion of beta-LCAT.

Abetalipoproteinemia↗

PubMed1988

Lipoprotein metabolism in hepatic lipase deficiency: studies on the turnover of apolipoprotein B and on the effect of hepatic lipase on high density lipoprotein.

Hepatic lipase deficiency produces significant distortion in the plasma lipoprotein profile. Particles with reduced electrophoretic mobility appear in very low density lipoprotein (VLDL). Intermediate density lipoprotein (IDL) increases markedly in the circulation and plasma low density lipoprotein (LDL) levels fall. At the same time there is a mass redistribution within the high density lipoprotein (HDL) spectrum leading to dominance in the less dense HDL2 subfraction. The present study examines apolipoprotein B turnover in a patient with hepatic lipase deficiency. The metabolism of large and small very low density lipoproteins was determined in four control subjects and compared to the pattern seen in the patient. Absence of the enzyme did not affect the rate at which large very low density lipoproteins were converted to smaller particles within this density interval (i.e., of VLDL). However, subsequent transfer of small very low density lipoproteins to intermediate density particles was retarded by 50%, explaining the abnormal accumulation of VLDL in the patient's plasma. Despite this, intermediate density particles accumulated to a level 2.4-times normal because their subsequent conversion to low density lipoprotein has been almost totally inhibited. Consequently, the plasma concentration of low density lipoprotein was only 10% of normal. On the basis of these observations, hepatic lipase appears to be essential for the conversion of small very low density and intermediate density particles to low density lipoproteins. The pathways of direct plasma catabolism of these species were not affected by the enzyme defect. In vitro studies were performed by adding purified hepatic lipase to the patient's plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

The isolation and characterisation of a cDNA clone for human lecithin:cholesterol acyl transferase and its use to analyse the genes in patients with LCAT deficiency and fish eye disease.

We have isolated cDNA clones coding for human lecithin:cholesterol acyl transferase (LCAT) from a liver-specific cDNA library by the use of two oligonucleotide probes based on the protein sequence. The clones span the sequence coding for the entire secreted LCAT, the 3' untranslated sequence and 12 amino acids of the signal peptide. The peptide sequence contains the conserved active site of serine lipases within a hydrophobic domain, flanked by a possible amphipatic alpha-helix. Only one gene for LCAT could be detected in genomic blots. We have used the cDNA as a probe to analyse the LCAT gene in patients suffering from LCAT deficiency and fish eye disease. No rearrangements or abnormal gene fragments were detected in these patients.

Amino Acid Sequence↗

PubMed1987

Net lipid transfer between lipoproteins in fish-eye disease plasma supplemented with normal high density lipoproteins.

Native fish-eye disease plasma, which is deficient of both high density lipoproteins (HDL) and lecithin-cholesterol acyltransferase activity (alpha-LCAT), processing the free cholesterol of these lipoproteins, has been supplemented with normal isolated HDL2 or HDL3 and incubated in vitro at 37 C. After incubation for 0, 7.5 and 24 hr the very low density (VLDL) and low density (LDL) lipoproteins as well as HDL were isolated, and their contents of triglycerides, phospholipids and free, esterified and total cholesterol were quantified. The resulting net mass transfer of the different lipids revealed a functioning transfer of cholesteryl esters and all other analyzed lipids between the lipoproteins, although no de novo esterification of the HDL cholesterol by LCAT in this plasma occurred. In accordance with previous findings there was a functioning esterification process of the free cholesterol of the combined VLDL and LDL of fish-eye disease plasma. The present reports make it reasonable to conclude that the lack of HDL cholesterol esterification in this disease is not a result of a deficiency of cholesteryl ester transfer or lipid transfer activities.

Cholesterol↗

PubMed1987

Increased removal rate of exogenous triglycerides after prolonged exercise in man: time course and effect of exercise duration.

Ten healthy young men exercised for 1.5 and 3 hours, respectively, 4 to 6 weeks apart at the same work intensity, corresponding to 77% of the individual maximal heart rate. In the fasting state 1 mL of 10% Intralipid/kg body weight was injected IV, the fractional removal rate was calculated (k2-value), and fasting lipid and apolipoprotein C-I, C-II, and CIII concentrations were determined one day before, immediately before, immediately after, and one day after the exercise: measurements were also made two and three days after the three-hour session. An increase of the k2-value was found only the day after the three-hour exercise (+66%, P less than .01), while after the 1.5-hour exercise the k2-value was not changed. One and two days after the three-hour exercise the fasting serum triglyceride concentration was significantly decreased by 33% and 16%, respectively. Serum triglyceride concentration was decreased also the day after the shorter session (-17%, P less than .05). Decreases in serum cholesterol concentrations were significant after both exercise bouts, but the significance disappeared if corrections for the changes in calculated plasma volume were made. Serum level of C apolipoproteins was decreased one day after the three-hour exercise, while it was not changed after the shorter exercise. This study shows that prolonged exercise produces an increase in the removal rate of Intralipid triglycerides from the bloodstream, that this change is related to the duration of exercise, and that some time is required following the exercise, before it is manifest.

Adult↗

PubMed1987

In vitro normalization of cholesteryl ester content and particle size of fish eye disease high density lipoproteins.

Isolated high density lipoprotein (HDL) from the two living fish eye disease patients have been incubated in vitro with autologous lipoprotein depleted plasma or with lipoprotein depleted plasma from domestic pig (Sus domesticus), with and without the presence of LCAT inhibitor for 24 hours at 0 and 37 degrees C. The lecithin:cholesterol acyltransferase (LCAT) activity in lipoprotein depleted pig plasma increased the abnormally low cholesteryl ester content of the fish eye disease HDL particles from about 20 to 100% and increased their exceptionally small mean particle size, probably by particle fusion, to a range which is representative of normal HDL3. Both esterification and particle enlargement were totally blocked by the LCAT inhibitor. Incubation of concentrated fish eye disease HDL with autologous lipoprotein depleted plasma for 24 hours at 37 degrees C resulted in a small increase in its cholesteryl ester percentage to 37%, without affecting the apparent HDL particle size. This finding confirms a deficiency of HDL lecithin:cholesterol acyltransferase activity (alpha-LCAT) in fish eye disease. The observed normalization of both HDL cholesteryl ester percentage and particle size by lipoprotein depleted pig plasma which contains virtually no cholesteryl ester transfer activity indicates that the latter is not a requisite for esterification of the free cholesterol of fish eye disease HDL.

Animals↗

PubMed1987

Inhibitory effect of normal high density lipoproteins on lecithin:cholesterol acyltransferase activity in fish eye disease plasma.

The lecithin:cholesterol acyltransferase (LCAT) activity of lipoprotein depleted normal and fish eye disease (FED) plasma was assayed in a modified Glomset-Wright incubation system where the enzyme was allowed to act on three different normal lipoprotein substrates consisting of an authentic mixture of very low (VLDL), low (LDL) and high (HDL) density lipoproteins to assay total LCAT activity, HDL to assay alpha-LCAT activity and combined VLDL and LDL to assay beta-LCAT activity, respectively. However, using normal plasma depleted of HDL, leaving its combined VLDL and LDL as enzyme substrate, resulted in a more than twofold increase in the LCAT activity of FED plasma from the two patients compared to the activity obtained with HDL present in the incubation mixture, indicating an inhibitory effect of HDL on the beta-LCAT activity present in FED plasma. This inhibitory effect of normal HDL could also be demonstrated by autoincubation of FED plasma mixed with isolated HDL2 or HDL3. Both these HDL subfractions had a pronounced inhibitory effect on the cholesteryl ester formation in FED plasma. The present study thus clearly demonstrates that normal HDL inhibits the beta-LCAT activity present in FED plasma, esterifying the free cholesterol of combined VLDL and LDL, derived from controls as well as from the two FED patients.

Corneal Opacity↗

PubMed1987

Different substrate specificities of plasma lecithin: cholesterol acyl transferase in fish eye disease and Tangier disease.

Esterification of plasma free cholesterol is mediated by lecithin:cholesterol acyl transferase (LCAT). The free cholesterol of plasma high density lipoproteins (HDL) is considered to be the preferred substrate for LCAT. It therefore appeared as a paradox that plasma cholesterol esterification, both in vivo and in vitro, is normal in fish eye disease and Tangier disease, two familial conditions with extremely low plasma HDL levels. Fish eye disease plasma, however, was shown to have LCAT activity primarily acting on combined very low (VLDL) and low (LDL) density lipoproteins, denominated beta-LCAT, while it lacked LCAT activity esterifying HDL cholesterol (alpha-LCAT). Here we show that Tangier plasma, in contrast, has both alpha- and beta-LCAT. Thus, in both fish eye and Tangier diseases it is beta-LCAT that explains the apparent normal plasma cholesterol esterification. We also show that Tangier plasma, having alpha-LCAT activity, normalizes the low cholesteryl ester content as well as the abnormally small size of fish eye disease HDL particles during incubation.

Cholesterol↗

PubMed1987

A long-term study on the effect of pindolol on serum lipoproteins: a preliminary report.

1. Preliminary results are reported from a long-term study aimed at recording the concentrations of serum lipids and lipoproteins at 6, 12 and 24 months of treatment with pindolol in young/middle-aged males with moderate hypertension. 2. Seventy-three patients have been recruited, of whom 47 have completed 6 months treatment. After 6 months treatment 35/47 patients had attained the target blood pressure of less than or equal to 95 mm Hg and analysis of plasma lipid and lipoprotein concentrations revealed a tendency for an increase of serum triglycerides and a lowering of low density lipoprotein cholesterol.

Adult↗

PubMed1987

Low A-esterase activity in serum of patients with fish-eye disease.

The activity of HDL-associated paraoxonase in the lipoprotein fraction of serum from two patients with fish-eye disease (FED) was only 11% of the mean value for control subjects. Similarly, concentrations of apolipoproteins A-I and A-II in the serum of FED subjects were only 10% of those in normal subjects. Thus the ratio of enzyme activity to A-I and A-II is virtually the same in these two groups of subjects. This suggests that paraoxonase activity of the lipoprotein fraction is associated with one or both of these apolipoproteins.

Apolipoprotein A-I↗